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Biomedical subjects

P Roger

Publications and source records attributed to P Roger.

At least 127 records · Page 7Linked to original sources
PubMed1990

Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma.

We evaluated the reliability of very low serum thyroglobulin (Tg) levels (less than 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of 131I therapy (99 patients), by performing whole body scans after a therapeutic course of 131I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 131I uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of 131I. In the majority of patients, especially those whose 131I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal.

Adenocarcinoma↗
PubMed1990

Plasma concentration of atrial natriuretic hormone during endogenous glucocorticoid hypercorticism.

In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.

ACTH Syndrome, Ectopic↗
PubMed1990

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: a comparison with the lysine-vasopressin test.

The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

Adolescent↗
PubMed1990

[Efficacy and long-term tolerance of ketoconazole in the treatment of Cushing's disease].

Successful short term treatment of patients with Cushing's disease by Ketoconazole without adverse effects is now well established. Little data are available about prolonged treatment of this disease with ketoconazole. We report herein our experience of ketoconazole therapy in four patients with Cushing's disease treated for 9 to 38 months. One patient rapidly developed adrenal hypofunction and required transient steroid therapy adjunction. In the other patients, cortisol overproduction was reduced to normal levels within two months and their urinary free cortisol remained within the normal range throughout the study. In two patients ketoconazole dose could be decreased but had to be increased after ten months of therapy in one patient. None of the patients had clinical or biochemical signs of drug toxicity. Thus, ketoconazole seems to be a useful drug for the prolonged metabolic control of Cushing's disease. However, in this circumstance, ketoconazole daily dose adaptation can be necessary in order to maintain normal urinary cortisol levels and the ability of ketoconazole to cure Cushing's disease still remains to be determined.

Adrenocorticotropic Hormone↗
PubMed1989

Pairs of cyclic AMP analogs, that are specifically synergistic for type I and type II cAMP-dependent protein kinases, mimic thyrotropin effects on the function, differentiation expression and mitogenesis of dog thyroid cells.

The role of the two different isozymes of the cAMP-dependent protein kinase is still unclear. We have investigated the potential roles for each isozyme in dog thyroid cells, a model in which the function, expression of differentiation and proliferation are positively regulated by thyrotropin acting through cyclic AMP. The dog thyroid contains both type I and type II cAMP-dependent protein kinases. These isozymes were selectively activated in vitro by type-I-directed and type-II-directed analog pairs. In thyroid slices, both type-I directed and type II-directed analog pairs synergistically activated thyroid hormone synthesis, as measured by incorporation of 131I into proteins and thyroid hormone secretion as determined by the release of butanol-extractable 131I. In primary cultures of dog thyroid cells both isozyme-directed analog pairs synergistically enhanced iodide trapping, a marker of differentiation, and DNA synthesis, as measured by the percentage of cells incorporating [3H]thymidine into their nuclei. However, DNA synthesis was more sensitive to type-I-directed pairs. The results demonstrate that both cAMP-dependent protein kinase isozymes can mediate the action of cAMP on function, differentiation expression and cell proliferation in dog thyroid cells.

Animals↗
PubMed1989

Protein synthesis during induction of DNA replication in thyroid epithelial cells: evidence for late markers of distinct mitogenic pathways.

The synthesis of specific protein has been investigated in primary cultures of dog thyroid epithelial cells, which can be induced to progress into G1 phase, in the presence of insulin, by different types of mitogens: thyrotropin (TSH) acting through cyclic adenosine monophosphate (cAMP), epidermal growth factor (EGF), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or 10% serum. EGF, TPA, or serum specifically induce [35S] methionine labeling of protein 1 (Mr approximately 80,000). The effect of EGF on protein 1 labeling and DNA replication is dependent on insulin. The level of protein 1 labeling as well as that of DNA synthesis is higher when TSH or TSH + serum are added together with EGF. It peaks in mid-G1. TSH alone, in the presence of insulin, stimulates DNA replication without inducing protein 1 synthesis, which thus represents a cell-cycle-dependent event that is not obligatory in mitogenic activation through cyclic AMP. Among the eight proteins whose synthesis is stimulated by TSH, only the labeling of protein 7, molecular weight ratio (Mr approximately 38,000), correlates with the DNA synthetic activity of the cells. The present authors identified protein 7 as cyclin/proliferating cell nuclear antigen (PCNA), the auxiliary protein of DNA polymerase-delta. The effect of TSH on cyclin synthesis is already detectable when most of the cells are in late G1, but its stimulation by EGF or EGF + serum is delayed and detected only after extending the labeling period to the S-phase. These data support the view that the cAMP-mediated mitogenic pathway remains partly distinct from the better known pathways induced by growth factors and tumor promoters, even at late stages of the G1-phase.

Animals↗
PubMed1989

Characterization of the anti-tumour activity against solid tumours of a new nitrosoureido sugar: Cy 233.

The anti-tumour properties of Cy 233, a new nitrosoureido sugar, were investigated in two murine solid tumours: B16 melanoma and subcutaneously implanted colon adenocarcinoma. Injected i.v., Cy 233 exerted a strong anti-tumour effect against the established B16 melanoma: long-term survivors were recorded with all schedules of treatment. The drug was even more effective against advanced colon 38 adenocarcinoma: it produced a high percentage of total tumour regression, regardless of the route of administration (i.p., i.v., p.o.). The marked in vivo activity of Cy 233 against advanced colon 38 adenocarcinoma, which is known to be resistant to such major anti-cancer drugs as BCNU and chlorozotocin, its water solubility and its stability in aqueous media are further elements warranting toxicological and clinical studies of this agent.

Adenocarcinoma↗
PubMed1989

Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.

Various new nitrosoureido derivatives of di- or trideoxy sugars were synthesized. The influence of the hydroxyl substitution pattern, the configuration at the anomeric center, and the absolute configuration of the sugar moiety on the antitumor activity of a series of nitrosoureido derivatives of di- and trideoxy sugars was studied. All compounds showed a very significant activity in vivo against L1210 leukemia, B16 melanocarcinoma, and Lewis lung carcinoma. Methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-2,3-dideoxy-alpha-D-arabino- hexopyranoside, 24 (NSC 609224), was found to be the most active compound. When treated with 24 (NSC 609224) at 20 mg/kg on day 1, at least 90% of the L1210 leukemia and B16 melanocarcinoma bearing mice showed a survival of over 60 days for a LD50 value for this compound of 42 mg/kg.

Amino Sugars↗
PubMed1989

[Value of the CRF test in primary and secondary adrenal insufficiency].

The ACTH and cortisol responses after CRF administration were studied in 21 patients with adrenal failure and compared with those obtained in 15 control subjects. In patients with Addison's disease, cortisol and ACTH responses were respectively abolished or excessive. In patients with secondary adrenal failure, a unique bolus injection of CRF allows the differentiation between pituitary or hypothalamic secretory defect. With regard to previous reports, the usefulness of CRF test in primary and secondary adrenal failure is stressed.

Addison Disease↗
PubMed1989

[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer].

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Mitogenic effects of thyrotropin and adenosine 3',5'-monophosphate in differentiated normal human thyroid cells in vitro.

Previous studies of human thyroid cells in culture (mostly from pathological tissues) failed to demonstrate a mitogenic effect of TSH, leading to the proposal that the growth effect of TSH in vivo might be indirect. To reexamine the influence of TSH on DNA synthesis and cell proliferation, we established primary cultures of normal thyroid tissue from nine subjects. When seeded in a 1% serum-supplemented medium, thyroid follicles released by collagenase/dispase digestion developed as a cell monolayer that responded to TSH by rounding up and by cytoplasmic retraction. When seeded in serum-free medium, the cells remained associated in dense aggregates surrounded by few slowly spreading cells. In the latter condition, the cells responded to TSH and other stimulators of cAMP production, such as cholera toxin and forskolin, by displaying very high iodide-trapping levels. Exposure to serum irreversibly abolished this differentiated function. TSH stimulated the proliferation (as shown by DNA content per culture dish) of 1% serum cultured cells (doubling times were reduced from 106 to 76 h) and increased by 100% the [3H]thymidine labeling indices. In serum-free cultured cells (dense aggregates or cell monolayers after initial seeding with serum), control levels of DNA synthesis were lower, and up to 8-fold stimulation of DNA synthesis occurred in response to 100 mU/L TSH (stimulation was consistently detected with 20 mU/L), based on measurements of [3H]thymidine incorporation into acid-precipitable material and counts of labeled nuclei on autoradiographs (up to 40% labeled nuclei within 24 h). The mitogenic effect of TSH required a high insulin concentration (8.3 X 10(-7) mol/L) or a low insulin-like growth factor I concentration. The mitogenic effects of TSH were mimicked in part by cholera toxin, forskolin, and dibutyryl cAMP. Epidermal growth factor and phorbol myristate ester also stimulated thyroid cell proliferation and DNA synthesis, but they potently inhibited TSH-stimulated iodide transport. We conclude that TSH, acting at least in part through cAMP, is a potent growth factor for human thyroid cells and thus provide an experimental basis in vitro for the well established in vivo goitrogenic action of TSH.

Adenosine Monophosphate↗
PubMed1988

The electrophysiological effects of thyrotropin-releasing hormone are similar in human TSH- and prolactin-secreting pituitary cells.

We studied the electrophysiological properties of individually characterized TSH-secreting cells cultured from pituitary fragments surgically removed from three patients, two who had primary TSH-secreting adenomas and one who had chronic TSH hypersecretion (hyperplasia) secondary to primary hypothyroidism. The TSH-secreting cells were excitable and had calcium-dependent action potentials. More than 80% of the cells cultured from the two patients with TSH-secreting adenomas were spontaneously active, whereas fewer cells (20%) cultured from the hypothyroid patient were spontaneously active. TRH (50 nmol/L) induced a complex pattern of electrical changes. The initial response was transient hyperpolarization (activation of potassium conductance), followed by increased low amplitude voltage fluctuations occasionally leading to action potentials. These TRH-induced electrophysiological changes were similar to those reported in rat and human PRL-secreting adenoma cells. These results suggest that TRH may have an identical mode of action in tumoral PRL and TSH cells. In the cells from the hypothyroid patient, the initial response to TRH cells was similar, but the second phase response was greater. The findings that the cells cultured from these patients behaved differently with regard to their electrophysiological characteristics (action potentials) and responses to TRH may reflect the different clinical conditions from which they were derived.

Action Potentials↗